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Novel combination therapy for AML based on CD44-mediated co-delivery of Daunorubicin, Cytarabine, and CD47 siRNA

Li, Qinzhe (2023) Novel combination therapy for AML based on CD44-mediated co-delivery of Daunorubicin, Cytarabine, and CD47 siRNA. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

The conventional “7+3” treatment regimen of daunorubicin and cytarabine has been a mainstay treatment for acute myeloid leukemia (AML) patients. However, one major limitation is the rapid elimination of the free drugs, resulting in the requirement of continuous drug infusion. A novel liposomal formulation of daunorubicin and cytarabine, CPX-351, was approved by FDA in 2017, which improved the survival outcome among elder patients, but the system lacks selective targeting of AML cells. CD47 is highly expressed in AML cells and serves as a “don’t eat me” signal to halt the phagocytosis upon binding with the SINPα receptors on macrophages. Antibodies that target CD47 can facilitate the phagocytosis of AML cells by macrophages but are associated with several adverse effects in animal studies including acute anemia. Here, a novel nanocarrier (PMBOP) is evaluated for the co-delivery of daunorubicin, cytarabine, and CD47 siRNA. With the ability to target CD44 on AML cells, we seek to improve the therapeutic outcome of AML treatment by increasing the bioavailability and reducing off-target effects.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Li, Qinzheqil94@pitt.eduqil94
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairLi, Songsol4@pitt.edu
Committee MemberMa, XiaochaoMXIAOCHA@pitt.edu
Committee MemberBrixius, Simonesib51@pitt.edu
Date: 4 May 2023
Date Type: Publication
Defense Date: 11 April 2023
Approval Date: 4 May 2023
Submission Date: 18 April 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 35
Institution: University of Pittsburgh
Schools and Programs: School of Pharmacy > Pharmaceutical Sciences
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Leukemia
Date Deposited: 04 May 2023 16:12
Last Modified: 04 May 2023 16:12
URI: http://d-scholarship.pitt.edu/id/eprint/44590

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